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Biomedical subjects

H Park

Publications and source records attributed to H Park.

At least 19 recordsLinked to original sources

Rupture of splenic artery aneurysm.

Three cases of death from splenic artery aneurysm rupture were encountered from 1988 to 1991 at the Philadelphia Medical Examiner's Office. In two cases, cocaine was detected in the blood and was believed to have precipitated the rupture. Toxicologic testing for cocaine should be performed in all cases of splenic artery aneurysm rupture and its presence should be interpreted properly as contributory rather than incidental to death.

Adult

Human immunodeficiency virus type 1 Rev activation can be achieved without Rev-responsive element RNA if Rev is directed to the target as a Rev/MS2 fusion protein which tethers the MS2 operator RNA.

The posttranscriptional trans activation of unspliced or partially spliced human immunodeficiency virus RNAs by the Rev regulatory protein is crucial for virus replication and is dependent on sequence-specific RNA binding by Rev. The cognate RNA target of Rev is contained within a highly structured, 244-nucleotide Rev-responsive element (RRE) RNA in the viral env gene. Here, we show that specific interaction with the RRE is not an absolute requirement for Rev function. When the RRE is replaced by a heterologous MS2 phage operator sequence, Rev will facilitate the cytoplasmic expression of human immunodeficiency virus mRNAs containing this sequence if directed to the MS2 operator via the RNA binding motif of the MS2 phage coat protein (MS-C) as a Rev/MS-C fusion protein. Rev/MS-C efficiently activated both RRE and MS2 targets. A mutation in the MS2 operator that abolished the coat protein binding in vitro rendered the mutant RNA nonresponsive to the fusion protein in vivo. Notwithstanding that Rev can be tethered to the viral RNAs via another RNA binding motif, the structural integrity of the N terminus of Rev was still required for optimal trans activation.

Animals

Study on the prevention of surface-induced platelet activation by albumin coating.

To understand how albumin on the surface inhibits surface-induced platelet activation, we adsorbed albumin on dimethyldichlorosilane-coated glass (DDS-glass) and modified the adsorbed albumin by three different methods. The adsorbed albumin was crosslinked with glutaraldehyde, dried and rehydrated, or digested with trypsin. Surface albumin concentration did not change by crosslinking; however, it decreased by about 15% by a simple dry-and-rehydration process. Trypsin digestion reduced the surface albumin concentration by 50%. Platelets were found to adhere and activate on albumin coated DDS-glass, if the adsorbed albumin was modified. The extent of platelet activation was quantified with two numeric parameters, the spread area and circularity. Fibrinogen adsorption to the dried or digested albumin layer resulted in enhancement of platelet activation, while adsorption of more albumin inhibited platelet activation. The results suggest that albumin can inhibit platelet activation as long as it covers the surface completely and remains flexible on the surface. This study indicates that steric repulsion is one of the mechanisms of surface passivation by albumin.

Adsorption

Benign granular cell tumor mimicking carcinoma of the breast. Report of a case.

A case of granular cell tumor of the breast in a 59 year-old woman is presented. Clinical evaluation suggested carcinoma with infiltration of the skin. The granular cell tumor was diagnosed on frozen section and the lesion was treated by wide local excision including the overlying skin. Granular cell tumors of the breast, which are usually benign, may closely mimic breast carcinoma, both clinically and on frozen section. The possibility of granular cell tumor of the breast with its potential for a false-positive diagnosis on frozen section supports a two-step procedure for the treatment of breast cancer, especially in young women, to prevent inappropriate radical surgery.

Adult

Genomic structure of human lysosomal glycosylasparaginase.

The gene structure of the human lysosomal enzyme glycosylasparaginase was determined. The gene spans 13 kb and consists of 9 exons. Both 5' and 3' untranslated regions of the gene are uninterrupted by introns. A number of transcriptional elements were identified in the 5' upstream sequence that includes two putative CAAT boxes followed by TATA-like sequences together with two AP-2 binding sites and one for Spl. A 100 bp CpG island and several ETF binding sites were also found. Additional AP-2 and Sp1 binding sites are present in the first intron. Two polyadenylation sites are present and appear to be functional. The major known glycosylasparaginase gene defect G488----C, which causes the lysosomal storage disease aspartylglycosaminuria (AGU) in Finland, is located in exon 4. Exon 5 encodes the post-translational cleavage site for the formation of the mature alpha/beta subunits of the enzyme as well as a recently proposed active site threonine, Thr206.

Acetylglucosamine

The minimum surface fibrinogen concentration necessary for platelet activation on dimethyldichlorosilane-coated glass.

Albumin and fibrinogen were competitively adsorbed onto dimethyldichlorosilane-coated glass (DDS-glass) and platelet activation was examined as a function of the surface fibrinogen concentration. The weight ratio of albumin to fibrinogen in the adsorption solution was varied from 10 to 700. Platelet activation was quantitated by the area and circularity of spread platelets. When the DDS-glass was coated with albumin alone, platelets were only contact adherent and could not spread at all. After competitive adsorption of fibrinogen and albumin, however, platelets were able to spread on the surface. Platelet activation increased linearly as the surface fibrinogen concentration increased up to 0.02 micrograms/cm2. Platelets were able to activate fully if the surface fibrinogen concentration was 0.02 micrograms/cm2 or higher, even though the surface was dominated by albumin. It appears that platelets can activate fully as long as only a small fraction (2-15%) of the surface is covered with tightly bound fibrinogen.

Adsorption

Differential activation of potato 3-hydroxy-3-methylglutaryl coenzyme A reductase genes by wounding and pathogen challenge.

Potato genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) were expressed in response to pathogen, elicitor, and wounding. HMGR catalyzes the rate-limiting step in isoprenoid biosynthesis leading to accumulation of phytoalexins and steroid glycoalkaloids. Wounding caused increases in HMGR mRNA levels. A rapid and transient peak occurred 30 minutes after wounding, followed by a slower peak at 14 hours; both were correlated with increased enzyme activity. Induction of HMGR mRNA by the soft rot pathogen Erwinia carotovora subsp carotovora or arachidonic acid began 8 hours after challenge and continued through 22 hours. Potato HMGR is encoded by a gene family. An HMGR gene-specific probe was used to demonstrate that one isogene of the HMGR family is pathogen activated and is distinct from isogene(s) that are wound activated. This provides evidence that defense-related increases in HMGR activity are due to mRNA level increases and that HMGR isogenes are activated differentially by wounding or pathogen challenge.

Arachidonic Acids

Morphological characterization of surface-induced platelet activation.

Morphological changes of platelets activated on glass and dimethyldichlorosilane-treated glass were investigated using video microscopy. The platelet morphological changes were quantified by measuring the area and circularity of spreading platelets. In addition, re-organization of cytoskeletal structures of spread platelets was examined. The effects of precoated albumin and fibrinogen on the platelet spreading kinetics were examined as a function of surface protein concentrations. Results showed that platelet shape changes were very sensitive to the surface concentration of precoated proteins. In general, platelets on fibrinogen-precoated surfaces spread fully to a circular shape and developed an extensive inner filamentous zone. In the presence of albumin on the surface, however, platelets could not spread fully and the development of the inner filamentous zone was very poor. For both albumin and fibrinogen, the maximum effects of precoated proteins on platelet shape changes were observed when the surface protein concentration reached the monolayer concentration.

Adsorption

Increase in glucose-stimulated insulin release and insulin biosynthesis in isolated pancreatic islets from D-galactosamine-treated rats.

Insulin secretion in response to glucose, glucose-stimulated insulin biosynthesis and insulin content was studied in pancreatic islets freshly isolated from male Wistar rats (150-200 g) with galactosamine-induced hepatitis. Animals were sacrificed by decapitation 3, 6, 12 and 24 hours after a single intraperitoneal injection of 500 mg/kg of galactosamine. Isolated islets prepared by collagenase method were perifused in Swim's medium with 20 mM glucose at 37 degrees C up to 30 minutes. Samples were taken at 2-10 min intervals for insulin assay. Insulin biosynthesis was assessed by the incorporation of [3H]-leucine into immunoprecipitable products (insulin and proinsulin) in pancreatic islets after 120 min incubation with 20 mM glucose. Glucose-stimulated insulin secretion was significantly increased at 6, 12 and 24 hours following the administration of galactosamine compared to control. The rate of insulin biosynthesis was stimulated to 170, 138 and 185% of control level 3, 6 and 12 hours after galactosamine-treatment, respectively. Significant increase in insulin content of islets was found 24 hours after galactosamine treatment, following the increased insulin biosynthesis. The present results indicate that pancreatic B cell function is activated in early stage of acute liver injury.

Alanine Transaminase

Suicide by captopril overdose.

We report a case of a 75 year-old male who committed suicide by taking an overdose of captopril. He took approximately ninety 12.5 mg captopril tablets. The postmortem plasma concentration of captopril was 60.4 mg/L. A review of the medical literature revealed five cases of captopril overdose all from unsuccessful suicide attempts. To our knowledge, this is the first case report of fatal captopril overdose with the measurement of plasma concentration of the drug.

Aged

Immunophenotypic spectrum of plasma cell leukemia.

Four cases of plasma cell leukemia (PCL) are reported that illustrate the variable immunotype of this disorder in contrast with the immunologic profile described for normal B-cell maturation and typical multiple myeloma (MM). Mature B-lymphocytes express B1 antigen (Ag) and surface immunoglobulin (SIg) whereas maturation to the plasma cell stage is accompanied by loss of these immunologic markers and expression of T10 Ag, plasma cell Ag (PCA), and cytoplasmic immunoglobulin (CIg). Plasma cells from patients with MM have previously been found to express the immunophenotype of normal plasma cells. In contrast, none of the four cases reported here express an immunologic profile typical for specific B-cell differentiation stages. Only one of four cases was strongly positive for PCA but additionally expressed B1 Ag and SIg. Of the remaining three cases, all expressed T10 Ag and CIg; two cases also expressed SIg, weak PCA, and B1 Ag. All four cases were monoclonal for lambda light chains and negative for common ALL Ag (CALLA). The variable expression of mature B-cell markers and plasma cell markers demonstrates the immunophenotypic spectrum of PCL; the prognostic significance of this heterogeneity needs to be more closely examined.

Adult

CHAPS solubilization of a G-protein sensitive 5-HT1A receptor from bovine hippocampus.

The binding of [3H] 8-OH-DPAT to membrane-bound 5-HT1A receptors from bovine hippocampus was saturable and corresponded to a single high-affinity state. Solubilization of the bovine hippocampal membranes with 10 mM CHAPS containing 200 mM NaCl, renders a preparation which binds [3H] 8-OH-DPAT with high-affinity (Kd = 1.9 nM) and is guanine nucleotide sensitive and ketanserin insensitive. 50% of [3H] 8-OH-DPAT binding activity is solubilized. The presence of GMP-P(NH)P promotes a low-affinity (Kd = 9.6 nM) state which is characteristic of receptors coupled to G-proteins. GMP-P(NH)P markedly accelerates the dissociation [3H] 8-OH-DPAT from solubilized membranes while having negligible effects on association. Thus, the agonist can activate the terniary complex rather than to promote its formation. 8-OH DPAT, WB 4101 and 5-carboxamidotryptamine dose responsively inhibit soluble [3H] 8-OH-DPAT binding with IC(50) values of 16.1, 15.6 and 1.3 nM, respectively. The CHAPS solubilized membrane preparation retains many of the [3H] 8-OH-DPAT binding characteristics of the membrane bound form.

8-Hydroxy-2-(di-n-propylamino)tetralin

Application of video-enhanced interference reflection microscopy to the study of platelet-surface interactions.

Video-enhanced interference reflection microscopy (VEIRM) was used to examine contact sites between the ventral membrane of intact platelets and underlying surfaces. It was observed that the ventral membrane in the central granulomere region of fully spread platelets was separated from the surface, while the membrane in other regions was mostly in close contact. The VEIRM image of intact platelets was compared with the video-intensified fluorescence microscopic (VIFM) image of cytoskeletal structures labeled with rhodamine-phalloidin. The VEIRM was also used to visualize the cytoskeletal structures of platelets spread on glass surfaces. Platelets were treated with Triton X-100, glutaraldehyde and acetic acid in sequence. This method was used to follow the sequence of cytoskeletal reorganization of platelets after surface-induced activation. In addition, the effects of albumin and fibrinogen on the cytoskeletal reorganization of spreading platelets were investigated. On fibrinogen-coated surfaces, platelets developed extensive inner filamentous zones which encircled the central granulomere region. In the presence of albumin, however, platelet inner filamentous zones were very poorly developed.

Actins

Mechanisms of mucoadhesion of poly(acrylic acid) hydrogels.

It has been proposed that mucoadhesives which adhere to the gastric mucus layer may be used to prolong gastric retention time of oral dosage forms. Preliminary studies, using acrylic hydrogels, have established that the density of carboxyl groups on the polymer chain is important for mucoadhesion. To understand the role(s) of the carboxyl groups in mucoadhesion, acrylic acid-acrylamide random copolymers [P(AA-co-AM)] were synthesized, and the adhesion strength of the cross-linked polymers to the gastric mucus layer was examined as a function of the pH, initial concentration of the cross-linking agent, degree of swelling, and carboxyl-group density. From the study on mucoadhesion of various P(AA-co-AM), it was found that at least 80% of the vinyl groups of the polymer must possess carboxyl groups in the protonated form. The dependence of mucoadhesion on pH and carboxyl-group density suggests that mucoadhesion occurs through hydrogen bonding. In addition, the density of the cross-linking agent significantly affects mucoadhesion. As the density of the cross-linking agent is lowered, the mucoadhesive strength increases, although the density of carboxyl groups in the test surface area is reduced. It is concluded that for mucoadhesion to occur, polymers must have functional groups that are able to form hydrogen bonds above the critical concentration (80% for vinyl polymers), and the polymer chains should be flexible enough to form as many hydrogen bonds as possible.

Acrylic Resins